Bone Disorders Flashcards
Osteoblasts
Bone forming cells, secrete bone matrix
Osteocytes
Mature bone cells enclosed by bone matrix
Osteoclasts
Resorbs bone, releasing Ca2+
Two Agents used to treat osteoporosis
Antiresorptive Drugs
- Decrease Bone Loss
Anabolic Agents
- Increase Bone Formation
What treats Rickets and Osteomalacia
Vitamin D Preparations
What treats Paget’s Disease
Bisphosphonates and Calcitonin
Bisphosphonates
- Examples
Aminobisphosphonates:
- Alendronate, Risedronate, Pamidronate, Zoledronate
Non-Aminobisphosphonates
- Etidronate, Clodronate
Bisphosphonates
- MOA
Inhibits osteoclast activity
- Aminobisphosphonates:
1. Disrupts the mevalonate pathway
2. Disrupts posttranslational modification of proteins
3. interrupting cellular signaling
4. interrupts osteoclast function
5. Leads to apoptosis of osteoclasts
- Non-Aminobisphosphonates
1. Accumulates cytotoxic metabolites within osteoclasts
2. Interferes with osteoclast function
3. Can lead to osteoclast cell death
Bisphosphonates
- Indication
- Osteoporosis
- Paget’s Disease
- Hypercalcemia
- Primary Hyperparathyroidism (Causes bone deminierlization)
Bisphosphonates
- Adverse Effects
- Gastrointestinal Issues
- Esophagitis Erosion
- Osteonecrosis of Jaw at high doses
- Aminobisphosphonates can cause a fever in first doses of IV administration
Estrogen (Bone Disorder)
- Examples
Raloxifene
Estrogen (Bone Disorder)
- MOA
Selective estrogen receptor modulators
- Stimulates osteoblasts
- Inhibits osteoclasts
Estrogen (Bone Disorder)
- Adverse Effects
- Hot flushes, flu-like symptoms
- Thrombophlebitis / Thromboembolism
Not recommended as a primary prevention of osteoporotic fracture
- Given to postmenopausal women who can not tolerate bisphosphonate
Parathyroid Hormone
- Examples
Teriparatide
Parathyroid Hormone
- MOA
- Increases Serum Calcium
- Decreases Serum Phosphate
- Increases RankL causing increased Osteoclast activity
Low Dose:
- Bone Formation
High Dose (Net effect):
- Bone Resorption
Parathyroid Hormone
- Acts on?
PTH acts on PTH-1 Receptors
PTH acts on osteoblasts
- Increases number of osteoblasts
- Inhibits apoptosis of osteoblasts
–> Bone Formation
PTH acts on Insulin-like growth factor (IGF-1) in osteoblasts
- Anabolic effect on bone
–>Bone Formation
PTH acts on the kidney:
- Increased Ca2+ and Mg2+ reabsorption
- Decreased phosphate, amino acids, bicarbonate, Na+, Cl-, Sulfate
- Stimulates 1,25 dihydroxyvitamin D
–> Creates more Vit D (Important for Bone Resorption)
Parathyroid Hormone
- Indication
Severe osteoporosis
- Or when bisphosphonates and SERM do not work
Parathyroid Hormone
- Contraindications
Children or young adults with open epiphysis
Hypercalcemia
Pregnancy
Paget’s Disease
History of radiation; risk of osteosarcoma
Parathyroid Hormone
- Adverse Effects
Mild Hypercalcemia
Leg Cramps
Nausea
Orthostatic Hypotension
Vitamin D
- MOA
Increases Calcium absorption from intestine, distal renal tubules,
Stimulates osteoblast (Form bone) and osteoclast (Dissolve bone)
Negative feedback: Results in decrease transcription of PTH
Result:
- Increases absorption of calcium allowing for stronger bones
- Increases muscle strength meaning less chances of falls and fractures
Vitamin D
- Indications
Osteoporosis
Hyperparathyroidism
Osteomalacia (Poor mineralization of bone)
RIckets (Lack of Vitamin D)
Vitamin D
- Side Effects
Hypercalcemia
- GI Pain
- Renal Stones
- Psychiatric Disturbances
RANKL Inhibitors
- Examples
Denosumab
RANKL Inhibitors
- MOA
- Inhibits RANKL on osteoblasts
- Prevents RANK (On Osteoclast) from binding RANKL (On Osteoblast)
- Prevents differentiation, activation, and survival of osteoclasts
- Inhibits osteoclast activity
Result: Decreased Bone Resorption
RANKL Inhibitors
- Indication
Osteoporosis
RANKL Inhibitors
- Side Effects
Eczema (Small risk)
Hypocalcemia
Increased Risk of Infection
Osteonecrosis of Jaw
Atypical Fractures
Calcitonin
- Examples
Salcatonin
Calcitonin
- MOA
Decreases reabsorption of calcium and phosphate in the kidney
Inhibits osteoclast activity
- Inhibits bone resorption
SC/IM
Calcitonin
- Indication
Hypercalcemia
Paget’s Disease (Less convenient to use, just use BP)
Postmenopausal and Corticosteroid related osteoporosis (Combined with other agents)
Calcium Salts
- Examples
Calcium Carbonate, Calcium Citrate, etc.
Calcium Salts
- MOA
Calcium and Vitamin D:
- Essential nutrients needed for bone health
Vitamin D increases absorption on Calcium
- Results in stronger bones
- Results in stronger muscles leading to less fall and fractures
Calcium Carbonate has the highest calcium
Calcium Salts
- Adverse Effects
Gastrointestinal Disturbances
Patients receiving Cardiac Glycosides (Extracellular Calcium Concentration can influence its toxicity)
